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Should you be worried about the declining birth rate?
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers. 
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers.
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers.
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Immunotherapies extend survival for melanoma patients with brain metastases
Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.
“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.
The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.
During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.
Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).
Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).
Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.
“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.
SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.
Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.
“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.
The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.
During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.
Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).
Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).
Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.
“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.
SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.
Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.
“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.
The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.
During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.
Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).
Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).
Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.
“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.
SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.
FROM CANCER IMMUNOLOGY RESEARCH
Key clinical point: Checkpoint blockade immunotherapy and BRAFV600-targeted therapy improve survival for patients with melanoma brain metastases.
Major finding: Patients with melanoma brain metastases receiving first-line checkpoint blockade immunotherapy had an improved 4-year overall survival (28.1% vs. 11.1%; P less than .001) and median overall survival (12.4 months vs. 5.2 months; P less than .001).
Study details: A retrospective study of 2,753 patients with stage IV melanoma and brain metastases, from the National Cancer Database, between 2010 and 2015.
Disclosures: The study was supported by the National Institute of Health, Abbvie, Bristol-Myers Squibb, Merck, and others. No conflicts of interest were reported.
Source: Iorgulescu et al. Cancer Immunol Res. 2018 July 12. doi: 10.1158/2326-6066.CIR-18-0067.
Depression screening rates remain low for undiagnosed adults
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
Depression screening among U.S. adults was 1.4% for the period from 2005 to 2015 despite a 2009 recommendation for routine screening from the U.S. Preventive Services Task Force, data from a cross-sectional study show.
In a brief report published online in Psychiatric Services, the researchers reviewed data from the National Ambulatory Medical Care Survey for the years 2005-2015. The study population included adults aged 18 and older without a previous history of depression. Overall, 105 million ambulatory care visits to nonpsychiatrists during the study period included depression screening. About two-thirds of the study population fell into the 18- to 64-year-old age range, 60% were women, 73% were white, and 89% lived in cities.
A multivariate analysis showed a significant increase in the likelihood of depression screening each year (odds ratio, 1.12), the researchers noted, and screening rates increased significantly in the years after 2009 in a piecewise regression analysis, Dr. Bhattacharjee and his associates reported.
The investigators also found links between the amount of time patients spent in physicians’ offices and higher screening rates. “Since increasing the length of time of the actual visit to the physician may be difficult, it is recommended that other health care providers in these settings be trained to provide screening,” they wrote.
The study was conducted before an updated USPSTF recommendation for screening regardless of the presence of enhanced services, the researchers noted, and “the low screening rate observed likely reflects the earlier recommendation,” they said. The findings were limited by several factors, including the cross-sectional study design that prevents causal inferences and the variation in depression screening methods, the researchers noted.
However, the results suggest that depression screening in primary care remains low – even in the years since the 2009 recommendation, they said.
Dr. Bhattacharjee disclosed no financial conflicts.
SOURCE: Bhattacharjee S et al. Psychiatr Serv. 2018 Jul 9. doi: 10.1176/appi.ps.201700439.
FROM PSYCHIATRIC SERVICES
T-DM1 produces 44% response rate in HER2-mutant lung cancers
Ado-trastuzumab emtansine (T-DM1) has met a predefined efficacy endpoint in what investigators say is the first positive clinical trial in patients with advanced HER2-mutant lung cancers.
The HER2-targeted therapy produced a 44% overall response rate among 18 patients enrolled in the phase 2, investigator-initiated basket trial reported in the Journal of Clinical Oncology.
The median progression-free survival (PFS) was 5 months in this heavily pretreated group of patients, according to first author Bob T. Li, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
“This is important therapeutic progress in the context of more than a decade of negative clinical trials targeting HER2 in lung cancer,” the researchers wrote.
The patients (median age, 64 years; 72% female) had metastatic lung adenocarcinomas treated in 2016 at Memorial Sloan Kettering Cancer Center. All patients had HER2-activating mutations identified by next-generation sequencing. They had received a median of two lines of prior therapy. Three of the 18 patients were treatment naive. Prior HER2-targeted therapy, including trastuzumab, was allowed.
All patients received intravenous infusions of T-DM1 at 3.6 mg/kg every 21 days until progression of disease or unacceptable toxicity.
Confirmed partial responses were seen in 8 patients (44%), while an additional 7 (39%) had stable disease, Dr. Li and his coauthors reported. Median PFS was 5 months overall and 6 months for responders, with the longest observed PFS being more than 11 months.
The treatment was well tolerated, with treatment-related adverse events mainly consisting of grade 1-2 infusion reactions, elevation of hepatic transaminases, and thrombocytopenia.
The rate of infusion reactions was higher than what was expected based on the experience with T-DM1 in breast cancer, though these reactions were generally mild and did not require discontinuation of the drug, which is approved for the treatment of HER2-amplified or –overexpressing metastatic breast cancer.
These findings have important implication for drug development in HER-2 mutant lung cancers, particularly as next-generation sequencing becomes more commonly used for initial tumor evaluation, Dr. Li and his coauthors noted.
“Just as the discovery of EGFR mutations eventually led to a plethora of approved oncogene-targeted therapies transforming the care of patients around the world, HER2-activating mutations similarly show promise as a therapeutic target,” they wrote.
Disappointing results were seen in previous studies looking at trastuzumab in lung cancer patients, and in those trials, patients were selected on the basis of HER2 protein expression by immunohistochemistry (IHC). “More recent studies have again confirmed that HER2 IHC is not the ideal biomarker in lung cancers,” the researchers wrote.
The 18-patient cohort in this study was part of a larger, investigator-initiated basket trial. Cohorts not reported at this time involved patients with other HER2-amplified solid tumors, including bladder.
The study was supported by the Conquer Cancer Foundation, Genentech, and a grant from the National Institutes of Health.
Dr. Li reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, and GRAIL. Several co-authors reported disclosures, including employment, with NantOmics, a developer of molecular profiling tools.
SOURCE: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.
Ado-trastuzumab emtansine (T-DM1) has met a predefined efficacy endpoint in what investigators say is the first positive clinical trial in patients with advanced HER2-mutant lung cancers.
The HER2-targeted therapy produced a 44% overall response rate among 18 patients enrolled in the phase 2, investigator-initiated basket trial reported in the Journal of Clinical Oncology.
The median progression-free survival (PFS) was 5 months in this heavily pretreated group of patients, according to first author Bob T. Li, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
“This is important therapeutic progress in the context of more than a decade of negative clinical trials targeting HER2 in lung cancer,” the researchers wrote.
The patients (median age, 64 years; 72% female) had metastatic lung adenocarcinomas treated in 2016 at Memorial Sloan Kettering Cancer Center. All patients had HER2-activating mutations identified by next-generation sequencing. They had received a median of two lines of prior therapy. Three of the 18 patients were treatment naive. Prior HER2-targeted therapy, including trastuzumab, was allowed.
All patients received intravenous infusions of T-DM1 at 3.6 mg/kg every 21 days until progression of disease or unacceptable toxicity.
Confirmed partial responses were seen in 8 patients (44%), while an additional 7 (39%) had stable disease, Dr. Li and his coauthors reported. Median PFS was 5 months overall and 6 months for responders, with the longest observed PFS being more than 11 months.
The treatment was well tolerated, with treatment-related adverse events mainly consisting of grade 1-2 infusion reactions, elevation of hepatic transaminases, and thrombocytopenia.
The rate of infusion reactions was higher than what was expected based on the experience with T-DM1 in breast cancer, though these reactions were generally mild and did not require discontinuation of the drug, which is approved for the treatment of HER2-amplified or –overexpressing metastatic breast cancer.
These findings have important implication for drug development in HER-2 mutant lung cancers, particularly as next-generation sequencing becomes more commonly used for initial tumor evaluation, Dr. Li and his coauthors noted.
“Just as the discovery of EGFR mutations eventually led to a plethora of approved oncogene-targeted therapies transforming the care of patients around the world, HER2-activating mutations similarly show promise as a therapeutic target,” they wrote.
Disappointing results were seen in previous studies looking at trastuzumab in lung cancer patients, and in those trials, patients were selected on the basis of HER2 protein expression by immunohistochemistry (IHC). “More recent studies have again confirmed that HER2 IHC is not the ideal biomarker in lung cancers,” the researchers wrote.
The 18-patient cohort in this study was part of a larger, investigator-initiated basket trial. Cohorts not reported at this time involved patients with other HER2-amplified solid tumors, including bladder.
The study was supported by the Conquer Cancer Foundation, Genentech, and a grant from the National Institutes of Health.
Dr. Li reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, and GRAIL. Several co-authors reported disclosures, including employment, with NantOmics, a developer of molecular profiling tools.
SOURCE: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.
Ado-trastuzumab emtansine (T-DM1) has met a predefined efficacy endpoint in what investigators say is the first positive clinical trial in patients with advanced HER2-mutant lung cancers.
The HER2-targeted therapy produced a 44% overall response rate among 18 patients enrolled in the phase 2, investigator-initiated basket trial reported in the Journal of Clinical Oncology.
The median progression-free survival (PFS) was 5 months in this heavily pretreated group of patients, according to first author Bob T. Li, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
“This is important therapeutic progress in the context of more than a decade of negative clinical trials targeting HER2 in lung cancer,” the researchers wrote.
The patients (median age, 64 years; 72% female) had metastatic lung adenocarcinomas treated in 2016 at Memorial Sloan Kettering Cancer Center. All patients had HER2-activating mutations identified by next-generation sequencing. They had received a median of two lines of prior therapy. Three of the 18 patients were treatment naive. Prior HER2-targeted therapy, including trastuzumab, was allowed.
All patients received intravenous infusions of T-DM1 at 3.6 mg/kg every 21 days until progression of disease or unacceptable toxicity.
Confirmed partial responses were seen in 8 patients (44%), while an additional 7 (39%) had stable disease, Dr. Li and his coauthors reported. Median PFS was 5 months overall and 6 months for responders, with the longest observed PFS being more than 11 months.
The treatment was well tolerated, with treatment-related adverse events mainly consisting of grade 1-2 infusion reactions, elevation of hepatic transaminases, and thrombocytopenia.
The rate of infusion reactions was higher than what was expected based on the experience with T-DM1 in breast cancer, though these reactions were generally mild and did not require discontinuation of the drug, which is approved for the treatment of HER2-amplified or –overexpressing metastatic breast cancer.
These findings have important implication for drug development in HER-2 mutant lung cancers, particularly as next-generation sequencing becomes more commonly used for initial tumor evaluation, Dr. Li and his coauthors noted.
“Just as the discovery of EGFR mutations eventually led to a plethora of approved oncogene-targeted therapies transforming the care of patients around the world, HER2-activating mutations similarly show promise as a therapeutic target,” they wrote.
Disappointing results were seen in previous studies looking at trastuzumab in lung cancer patients, and in those trials, patients were selected on the basis of HER2 protein expression by immunohistochemistry (IHC). “More recent studies have again confirmed that HER2 IHC is not the ideal biomarker in lung cancers,” the researchers wrote.
The 18-patient cohort in this study was part of a larger, investigator-initiated basket trial. Cohorts not reported at this time involved patients with other HER2-amplified solid tumors, including bladder.
The study was supported by the Conquer Cancer Foundation, Genentech, and a grant from the National Institutes of Health.
Dr. Li reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, and GRAIL. Several co-authors reported disclosures, including employment, with NantOmics, a developer of molecular profiling tools.
SOURCE: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Ado-trastuzumab emtansine (T-DM1) demonstrated activity in advanced, HER2-mutant lung cancer.
Major finding: Confirmed partial responses were seen in 44% of patients. Median progression-free survival was 5 months.
Study details: Analysis of a cohort of 18 patients with HER2-mutant metastatic lung adenocarcinomas enrolled in a phase 2, investigator-initiated basket trial.
Disclosures: The Conquer Cancer Foundation, Genentech, and the National Institutes of Health supported the study. The researchers reported disclosures related to Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Genentech, Illumina, BioMed Valley Discoveries, AstraZeneca, GRAIL, and NantOmics, among others.
Source: Li BT et al. J Clin Oncol. 2018 July 10. doi: 10.1200/JCO.2018.77.9777.
Inadvertent Perioperative Hypothermia During Orthopedic Surgery
ABSTRACT
Inadvertent perioperative hypothermia is a significant problem in patients undergoing either emergency or elective orthopedic surgery, and is associated with increased morbidity and mortality. Though in general the incidence of inadvertent perioperative hypothermia in postoperative recovery rooms has been decreasing over the last 2 decades, it still remains a significant risk in certain specialty practices, such as orthopedic surgery. This review article summarizes the currently available evidence on the incidence, risk factors, and complications of inadvertent perioperative hypothermia. Also, the effective preventive strategies in dealing with inadvertent perioperative hypothermia are reviewed and essential clinical guidelines to be followed are summarized.
Continue to: Inadvertent perioperative hypothermia...
Inadvertent perioperative hypothermia, defined as an involuntary drop in core body temperature to <35°C (95°F), is a condition associated with significant morbidity and mortality.1 This phenomenon has been reported in both emergency orthopedic admissions, such as fracture management, as well as in the elective setting such as arthroscopy, arthroplasty, and spine surgery.
In a study conducted in the United Kingdom including 781 elderly patients with a mean age of 80 years who presented with hip fractures, the 30-day mortality rate was 15.3% in patients who were admitted with a tympanic temperature of <36.5°C and only 5.1% in patients who maintained a tympanic temperature of 36.5°C to 37.5°C (odds ratio, 2.8; P > .0005).2 For an even better perspective, this analysis can be compared with the UK National Hip Fracture Database of 2013, which reported a 30-day mortality of 8.2% in patients who were admitted to the National Health Service with a diagnosis of hip fracture.3
Inadvertent perioperative hypothermia is also a common phenomenon during elective orthopedic hospital admissions. An Australian audit, which included 5050 postoperative patients, looked into the association between inadvertent perioperative hypothermia and mortality based on diagnostic criteria classifying mild hypothermia as a core temperature of <36°C and severe hypothermia as a core temperature of <35°C.4 The authors found that mild and severe hypothermia was experienced by 36% and 6% of patients, respectively. In-hospital mortality was 5.6% for normothermic patients, 8.9% for all hypothermic patients (P < .001), and 14.7% for severely hypothermic patients (P < .001). For a decrease of 1°C in core body temperature from <36°C to <35°C (but >34°C), there were higher odds of in-hospital mortality (odds ratio, 1.83; 95% confidence interval [CI], 1.20-2.60).
The physiologic response to hypothermia is to decrease heat loss by cutaneous and peripheral vasoconstriction and increase heat production by increasing the metabolic rate (eg, shivering and shifting to anaerobic metabolism). This response is blunted to a variable extent in perioperative patients for several reasons, including the effect of anesthetic drugs and old age.5
Maintenance of core body temperature >36°C is now a measured standard of perioperative care. A performance measure for perioperative temperature management was developed by the American Medical Association Physician Consortium for Performance Improvement (AMA-PCPI).6 To achieve this performance measure, mandatory documentation of use of active warming intraoperatively or a record of at least 1 body temperature ≥96.8°F (36°C) within 30 minutes immediately prior to and 15 minutes immediately after anesthesia end time is necessary. This performance measure is also endorsed by the Surgical Care Improvement Project (SCIP-Inf-10) and National Quality Forum (NQF).6
Continue to: Overall, in the last 2 decades...
Overall, in the last 2 decades, the incidence of inadvertent perioperative hypothermia has decreased, mainly due to aggressive intraoperative management.7 In spite of this, studies have shown that perioperative hypothermia remains a significant problem in patients undergoing orthopedic procedures. In a recent community hospital study conducted by the National Association for Healthcare Quality that included 4124 orthopedic patients undergoing elective surgery, it was shown that, in spite of 99% compliance to the AMA-PCPI recommendation, 7.7% of orthopedic patients were found to be hypothermic.6
Management of hypothermia has long been an integral component of “damage control surgery” and resuscitation during polytrauma, which aims to aggressively minimize hypovolemic shock and limit the development of the lethal triad of hypothermia, coagulopathy, and acidosis.8 However, critical references to prevention and management of inadvertent perioperative hypothermia are lacking in the orthopedic literature on elective surgical procedures. This review aims to bridge this knowledge gap.
Unless otherwise specified, inadvertent perioperative hypothermia in this article refers to the core body temperature. In contrast, peripheral/limb hypothermia refers primarily to the effect of tourniquet application to the involved limb and the effect after deflation of the tourniquet on core body temperature.
RISK FACTORS
There are several measurable risk factors that can contribute to inadvertent perioperative hypothermia, which can be subdivided into 3 groups: patient-related risk factors, anesthesia-related risk factors, and procedure-related risk factors (Table 1).5,9-11 It is important to note that in any given patient a combination of 2 or more risk factors predisposes them to developing inadvertent perioperative hypothermia. Conceptualizing the etiology of inadvertent perioperative hypothermia in this way helps to plan a multipronged strategy to prevent it from occurring in the first place. Some of the important risk factors for inadvertent perioperative hypothermia are discussed below.
Table 1. Risk Factors for Perioperative Hypothermia
Patient-Related Risk Factors | Anesthesia-Related Risk Factors | Procedure-Specific Risk Factors |
|
|
|
To identify patient-related risk factors, researchers from the University of Louisville conducted a study including 2138 operative patients who became hypothermic after admission, of whom 27% underwent orthopedic and spine procedures.9 The patient-related risk factors identified were a high severity of illness on admission (odds ratio, 2.81; 95% CI, 2.28-3.47), presence of a neurological disorder such as Alzheimer’s disease (odds ratio, 1.71; 95% CI,1.06-2.78), male sex (odds ratio, 1.65; 95% CI, 1.36-2.01), age >65 years (odds ratio, 1.61; 95% CI, 1.33-1.96), recent weight loss (odds ratio, 1.60; 95% CI, 1.04-2.48), anemia (odds ratio, 1.49; 95% CI, 1.12-1.98), and chronic renal failure (odds ratio, 1.43; 95% CI, 1.07-1.92). Interestingly, diabetes mellitus without end-stage organ failure was not found to be a significant risk factor (odds ratio, 0.58; 95% CI, 0.44-0.75). It is also important to note that some of these risk factors identified to contribute to perioperative hypothermia are dependent on each other and others are independent of each other. For example, chronic renal failure and anemia are dependent risk factors. In contrast, age >65 years and low body mass index as risk factors of perioperative hypothermia are independent of each other.
Continue to: The second subgroup of risk factors...
The second subgroup of risk factors for perioperative hypothermia is related to anesthesia. The effect of general and regional anesthesia on perioperative core temperature is significantly different, both in terms of intraoperative thermoregulation and postoperative recovery.12 Intraoperatively, the core body temperature during the first 2 hours of general anesthesia decreases at a rate of 1.3°C per hour due to loss of thermoregulatory cutaneous and peripheral vasoconstrictive responses resulting in heat loss exceeding metabolic heat production. However, the core temperature remains virtually constant during the subsequent 3 hours due to the return of the thermoregulatory response, which causes cutaneous and peripheral vasoconstriction and increased metabolic heat production. Postoperative recovery from the hypothermia induced by general anesthesia is significantly faster than from that induced by regional anesthesia.13
The effect of regional hypothermia on core body temperature is more complex because it must be considered in addition to the effect of an associated procedure-related variable (ie, tourniquet application). If a tourniquet is not used during a surgery with regional anesthesia, a linear decrease in core temperature follows until recovery, due to increased blood flow from the loss of sympathetic peripheral vasoconstrictive response with resultant core-to-peripheral heat redistribution to the exposed operating limb. If a tourniquet is used during surgery with regional anesthesia, there will be no significant effect of the exposed operating limb on core temperature, as there is no blood flow between them. However, once the tourniquet is deflated, the core body temperature will be affected significantly as a result of core-to-peripheral distribution of heat to the operated limb with the return of blood flow. This fall in core body temperature after tourniquet deflation can be prevented by active forced-air warming initiated from the beginning of surgery.10 The extent and rate of development of peripheral/limb hypothermia during surgery (and its subsequent effect on core body temperature) depends on several factors, including the operating room ambient temperature, duration of tourniquet application, and temperature of the irrigation fluid. Postoperative recovery from the hypothermia induced by regional anesthesia takes longer than from that induced by general anesthesia because of the prolonged period of loss of vasoconstrictive response.
The third subgroup of risk factors associated with perioperative hypothermia is procedure related. Several procedure-specific risk factors for inadvertent perioperative hypothermia during arthroscopic surgery are identified, including prolonged operating time, low blood pressure during the procedure, and low temperature of the irrigation fluid.11 It is logical to extrapolate the importance of these risk factors to other orthopedic procedures which also require prolonged operating times, are performed under hypotension, or expose the patient to irrigation fluid that is at a low temperature. Understanding the importance of each of these procedure-related risk factors is the most important from the perspective of the orthopedic surgeon when compared to the rest of the subgroups of risk factors for inadvertent perioperative hypothermia as he/she is directly responsible for them.
The ambient operating room temperature has traditionally been considered a risk factor for inadvertent hypothermia in perioperative patients, but evidence is available to the contrary. The recommended ambient room temperature as per the clinical guideline published by the American Society of PeriAnesthesia Nurses (ASPAN) is 20°C to 24°C (68°F-75°F).14 The ambient temperature can have a significant effect on peripheral/limb hypothermia when operating on a limb with a tourniquet inflated, as the limb has no blood supply to distribute heat from the core to the periphery. However, the direct effect of ambient room temperature on the patient’s core body temperature is unlikely to be clinically significant if standard active warming interventions are implemented.15
COMPLICATIONS
The increased incidence of mortality due to inadvertent hypothermia in the perioperative period has already been discussed. Several other complications of inadvertent perioperative hypothermia include increased incidence of coagulopathy, acidosis, stroke, sepsis, pneumonia, myocardial infarction, surgical site infections, altered drug metabolism, and longer hospital stays.8,9,16-18 Hypothermia, coagulopathy, and acidosis have long been recognized as a lethal triad more commonly seen in polytrauma patients than in elective orthopedic surgery, as this occurs at extremes of temperature, usually <32°C. When compared with patients who did not develop perioperative hypothermia, patients who developed hypothermia during elective operations were shown to experience an overall doubled complication rate (13.9% vs 26.3%; P < .001) of which the incidence of stroke (1.0% vs 6.5%; P < .001), pneumonia (1.3% vs 5.1%; P < .001), and sepsis (2.6% vs 7.5%; P < .001) were much more likely than myocardial infarction (1.1% vs 3.3%; P = .01) and wound infection (3.3% vs 5.0%; P = .14).9
Continue to: Prevention...
PREVENTION
Prevention of perioperative hypothermia is a core measure to improve the outcome after ambulatory and fast-track orthopedic surgery and rehabilitation. Preventive strategies for perioperative hypothermia can be grouped into passive heat retention methods and active external warming methods (Table 2). Passive methods aim to maintain body temperature by decreasing the heat loss by radiation (eg, reflective blanket), conduction (eg, layered cotton blankets and padding the operating table), or convection (eg, heat and humidity exchanger in the breathing circuits) to the surrounding environment. Active patient heating methods aim to bring in heat from the source to the patient’s body using conduction (eg, Hot Dog® [Eden Augustine Temperature Management]) or convection (eg, Bair Hugger® [Arizant Healthcare]) techniques.
Table 2. Methods to Prevent Inadvertent Perioperative Hypothermia
Passive Heat-Retention Methods | Active External Warming Methods |
| Conduction techniques:
Convection techniques:
|
Active patient warming is superior to passive heat retention methods. A recent Cochrane study assessed the effects of standard care (ie, use of layered clothing and warm blankets, etc.) and addition of extra thermal insulation by reflective blankets or active forced air warming to standard care on the perioperative core body temperature.19 They concluded that there is no clear benefit of addition of extra thermal insulation by reflective blankets compared with standard care alone. Also, forced-air warming in addition to standard care appeared to maintain core temperature better than standard care alone, by between 0.5°C and 1°C, but the clinical importance of this difference could not be inferred, as none of the included studies in this meta-analysis documented major cardiovascular outcomes.
Several clinical guidelines have been developed by not-for-profit, government, and professional organizations aimed at prevention of perioperative hypothermia as primary or secondary outcome. A clinical guideline was published by ASPAN in 2001 for assessment, prevention, and intervention in unplanned perioperative hypothermia.14 Cost and time effectiveness of the ASPAN Hypothermia Guideline was published in 2008.20 The assessment guideline includes identification of risk factors, repeated pre-/intra-/postoperative temperature measurement, and repeated clinical evaluation of the patient’s status. The preventive guideline is to maintain an ambient temperature of 20°C to 24°C (68°F-75°F) and use appropriate passive patient warming methods pre-, intra-, and postoperatively. Intervention in the form of active patient heating is advised only if the patient develops hypothermia in spite of the above-mentioned standard preventive measures. But many orthopedic ambulatory surgery centers currently use active patient warming as both a preventive and an intervention strategy.
Active patient warming by conduction devices occurs by direct physical contact with the device, which is set at a higher temperature, whereas heat transfer from the convection device to the patient occurs by a physical medium such as forced air or circulating water that moves in between the device and the patient. Any recommendation for use of a specific technique of active patient warming (ie, by the use of a conduction device or a convection device) should only be given after comparing evidence on 3 critical aspects: efficacy, safety, and cost effectiveness.
The heating efficacy and core rewarming rates of conduction and convection devices have been compared in the literature. Full-body forced-air heating with the Bair Hugger® and full-body resistive polymer heating with the Hot Dog® in healthy volunteers were found to be similar.21 Also, in a randomized study conducted on 80 orthopedic patients undergoing surgery, resistive polymer warming performed as efficiently as forced-air warming in patients undergoing orthopedic surgery.22
Continue to: Secondly, the safety of convection...
Secondly, the safety of convection devices such as the Bair Hugger® has been under intense scrutiny based on the evidence that it disrupts the laminar airflow in the operating theater.23-26 This disruption in laminar air flow has been shown to cause emission of significant levels of airborne contaminants of size >0.3 μm (germ size).27 Isolates of Staphylococcus aureus, coagulase-negative Staphylococcus species, and methicillin-resistant Staphylococcus aureus were detected in 13.5%, 3.9%, and 1.9% of forced-air blowers, respectively.28 However, the clinical effect on the rate of deep joint infection due to the disruption of laminar air flow has been examined in only 1 study. McGovern and colleagues29 reported a significant increase in deep joint infection during a period when forced air warming was used compared to a period when conductive fabric warming was used (odds ratio, 3.8; P = .024) and recommended air-free warming by a conduction device over forced-air warming for orthopedic procedures. Unfortunately, the prophylactic antibiotic regimen was not kept constant during their study period. During an overlapping time frame during which they shifted from the use of a convection device (Bair Hugger®) to a conduction device (Hot Dog®), they also changed their antibiotic regimen from gentamicin 4.5 mg/kg intravenous (IV) to gentamicin 3 mg/kg IV plus teicoplanin 400 mg IV. This change in antibiotic regimen is a major confounding factor that calls into question the validity of the conclusions drawn by the authors.
Finally, the cost effectiveness of conduction and convection devices has never been studied. Hence, based on the current evidence, it is not possible to recommend a particular type of active patient-warming device.
CONCLUSION
Orthopedic surgeons should be aware that inadvertent perioperative hypothermia is a common phenomenon in perioperative patients. It must be recognized that the maintenance of perioperative normothermia during all major orthopedic surgical procedures is desirable, as inadvertent perioperative hypothermia is shown to be associated with increased mortality and systemic morbidity, such as stroke and sepsis. Compliance with the current clinical guidelines for assessment, prevention, and treatment of inadvertent perioperative hypothermia will minimize, if not eliminate, such risk. We recommend the following essential clinical guidelines to prevent inadvertent perioperative hypothermia (Table 3). Identification of patient-, anesthesia-, and procedure-related risk factors is an integral component of assessment of the risk of inadvertent perioperative hypothermia. In order to achieve full compliance with implementation of active patient warming during surgery, it is prudent to make active warming information a part of the surgical timeout checklist. Irrespective of the presence of risk factors, passive heat retention methods should be part of perioperative management of patients undergoing elective orthopedic surgery to prevent inadvertent perioperative hypothermia. In addition, there should be a minimum threshold to utilize active patient-warming techniques, especially in patients with inherent risk factors and surgeries that take >30 minutes of operating time, either under regional or general anesthesia. As there are concerns about safety issues with the use of convection devices, we believe a multicenter randomized controlled trial is warranted.
Table 3. Recommended Essential Clinical Guidelines for Prevention of Inadvertent Perioperative Hypothermia
|
- Brown DJ, Brugger H, Boyd J, Paal P. Accidental Hypothermia. N Engl J Med. 2012;367(20):1930-1938. doi:10.1056/NEJMra1114208.
- Uzoigwe CE, Khan A, Smith RP, et al. Hypothermia and low body temperature are common and associated with high mortality in hip fracture patients. Hip Int. 2014; 24(3):237-242. doi:10.5301/hipint.5000124.
- Johansen A, Wakeman R, Boulton C, Plant F, Roberts J, Williams A. National Hip Fracture Database: National Report 2013. London, UK: National Hip Fracture Database, Royal College of Physicians; 2013.
- Karalapillai D, Story DA, Calzavacca, Licari E, Liu YL, Hart GK. Inadvertent hypothermia and mortality in postoperative intensive care patients: retrospective audit of 5050 patients. Anaesthesia. 2009;64(9):968-972. doi:10.1111/j.1365-2044.2009.05989.x.
- Horosz B, Malec-Milewska M. Inadvertent intraoperative hypothermia. Anaesthesiol Intensive Ther. 2013;45(1):38-43. doi:10.5603/AIT.2013.0009.
- Steelman VM, Perkhounkova YS, Lemke JH. The gap between compliance with the quality performance measure "perioperative temperature management” and normothermia. J Healthc Qual. 2014;37(6):333-341. doi:10.1111/jhq.12063.
- National Institute for Health and Clinical Excellence. Inadvertent Perioperative Hypothermia: The Management of Inadvertent Perioperative Hypothermia in Adults. London, UK: National Institute for Health and Clinical Excellence; 2008.
- Carlino W. Damage control resuscitation from major haemorrhage in polytrauma. Eur J Orthop Surg Traumatol. 2014;24(2):137-141. doi:10.1007/s00590-013-1172-7.
- Billeter AT, Hohmann SF, Druen D, Cannon R, Polk HC Jr. Unintentional perioperative hypothermia is associated with severe complications and high mortality in elective operations. Surgery. 2014;156(5):1245-1252. doi:10.1016/j.surg.2014.04.024.
- Kim YS, Jeon YS, Lee JA, et al. Intra-operative warming with a forced-air warmer in preventing hypothermia after tourniquet deflation in elderly patients. J Int Med Res. 2009;37(5):1457-1464. doi:10.1177/147323000903700521.
- Parodi D, Tobar C, Valderrama J, et al. Hip arthroscopy and hypothermia. Arthroscopy. 2012;28(7):924-928. doi:10.1016/j.arthro.2011.12.012.
- Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology. 1995;83(3):491-499.
- Vaughan MS, Vaughan RW, Cork RC. Postoperative hypothermia in adults: relationship of age, anesthesia, and shivering to rewarming. Anesth Analg. 1981;60(10):746-751.
- American Society of PeriAnesthesia Nurses. Clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):305-314.
- Inaba K, Berg R, Barmparas G, et al. Prospective evaluation of ambient operating room temperature on the core temperature of injured patients undergoing emergent surgery. J Trauma Acute Care Surg. 2012;73(6):1478-1483. doi:10.1097/TA.0b013e3182781db3.
- Barie PS. Surgical site infections: epidemiology and prevention. Surg Infect (Larchmt). 2002;3 Suppl 1:S9-S21. doi:10.1089/sur.2002.3.s1-9.
- Jeran L. Patient temperature: an introduction to the clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):303-304.
- Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334(19):1209-1215.
- Alderson P, Campbell G, Smith AF, Warttig S, Nicholson A, Lewis SR. Thermal insulation for preventing inadvertent perioperative hypothermia. Cochrane Database Syst Rev. 2014;6:CD009908. doi:10.1002/14651858.CD009908.pub2.
- Berry D, Wick C, Magons P. A clinical evaluation of the cost and time effectiveness of the ASPAN Hypothermia Guideline. J Perianesth Nurs. 2008;23(1):24-35. doi:10.1016/j.jopan.2007.09.010.
- Kimberger O, Held C, Stadelmann K et al. Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers. Anesth Analg. 2008;107(5):1621-1626. doi:10.1213/ane.0b013e3181845502.
- Brandt S, Oguz R, Hüttner H, et al. Resistive-polymer versus forced-air warming: comparable efficacy in orthopedic patients. Anesth Analg. 2010;110(3):834-838. doi:10.1213/ANE.0b013e3181cb3f5f.
- Legg AJ, Hammer AJ. Forced-air patient warming blankets disrupt unidirectional airflow. Bone Joint J. 2013;95-B(3):407-410. doi:10.1302/0301-620X.95B3.29121.
- Dasari KB, Albrecht M, Harper M. Effect of forced-air warming on the performance of operating theatre laminar flow ventilation. Anaesthesia. 2012;67(3):244-249. doi:10.1111/j.1365-2044.2011.06983.x.
- Belani KG, Albrecht M, McGovern PD, Reed M, Nachtsheim C. Patient warming excess heat: the effects on orthopedic operating room ventilation performance. Anesth Analg. 2013;117(2):406-411. doi:10.1213/ANE.0b013e31825f81e2.
- Legg AJ, Cannon T, Hammer AJ. Do forced air patient-warming devices disrupt unidirectional downward airflow? J Bone Joint Surg Br. 2012;94(2):254-256. doi:10.1302/0301-620X.94B2.27562.
- Albrecht M, Gaithier RL, Belani K, Litchy M, Leaper D. Forced-air warming blowers: An evaluation of filtration adequacy and airborne contamination emissions in the operating room. Am J Infect Control. 2011;39(4):321-328. doi:10.1016/j.ajic.2010.06.011.
- Reed M, Kimberger O, McGovern PD, Albrecht MC. Forced-air warming design: evaluation of intake filtration, internal microbial buildup, and airborne-contamination emissions. AANA J. 2013;81(4):275-280.
- McGovern PD, Albercht M, Belani KG, et al. Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics. J Bone Joint Surg Br.2011;93(11):1537-1544. doi:10.1302/0301-620X.93B11.27124.
ABSTRACT
Inadvertent perioperative hypothermia is a significant problem in patients undergoing either emergency or elective orthopedic surgery, and is associated with increased morbidity and mortality. Though in general the incidence of inadvertent perioperative hypothermia in postoperative recovery rooms has been decreasing over the last 2 decades, it still remains a significant risk in certain specialty practices, such as orthopedic surgery. This review article summarizes the currently available evidence on the incidence, risk factors, and complications of inadvertent perioperative hypothermia. Also, the effective preventive strategies in dealing with inadvertent perioperative hypothermia are reviewed and essential clinical guidelines to be followed are summarized.
Continue to: Inadvertent perioperative hypothermia...
Inadvertent perioperative hypothermia, defined as an involuntary drop in core body temperature to <35°C (95°F), is a condition associated with significant morbidity and mortality.1 This phenomenon has been reported in both emergency orthopedic admissions, such as fracture management, as well as in the elective setting such as arthroscopy, arthroplasty, and spine surgery.
In a study conducted in the United Kingdom including 781 elderly patients with a mean age of 80 years who presented with hip fractures, the 30-day mortality rate was 15.3% in patients who were admitted with a tympanic temperature of <36.5°C and only 5.1% in patients who maintained a tympanic temperature of 36.5°C to 37.5°C (odds ratio, 2.8; P > .0005).2 For an even better perspective, this analysis can be compared with the UK National Hip Fracture Database of 2013, which reported a 30-day mortality of 8.2% in patients who were admitted to the National Health Service with a diagnosis of hip fracture.3
Inadvertent perioperative hypothermia is also a common phenomenon during elective orthopedic hospital admissions. An Australian audit, which included 5050 postoperative patients, looked into the association between inadvertent perioperative hypothermia and mortality based on diagnostic criteria classifying mild hypothermia as a core temperature of <36°C and severe hypothermia as a core temperature of <35°C.4 The authors found that mild and severe hypothermia was experienced by 36% and 6% of patients, respectively. In-hospital mortality was 5.6% for normothermic patients, 8.9% for all hypothermic patients (P < .001), and 14.7% for severely hypothermic patients (P < .001). For a decrease of 1°C in core body temperature from <36°C to <35°C (but >34°C), there were higher odds of in-hospital mortality (odds ratio, 1.83; 95% confidence interval [CI], 1.20-2.60).
The physiologic response to hypothermia is to decrease heat loss by cutaneous and peripheral vasoconstriction and increase heat production by increasing the metabolic rate (eg, shivering and shifting to anaerobic metabolism). This response is blunted to a variable extent in perioperative patients for several reasons, including the effect of anesthetic drugs and old age.5
Maintenance of core body temperature >36°C is now a measured standard of perioperative care. A performance measure for perioperative temperature management was developed by the American Medical Association Physician Consortium for Performance Improvement (AMA-PCPI).6 To achieve this performance measure, mandatory documentation of use of active warming intraoperatively or a record of at least 1 body temperature ≥96.8°F (36°C) within 30 minutes immediately prior to and 15 minutes immediately after anesthesia end time is necessary. This performance measure is also endorsed by the Surgical Care Improvement Project (SCIP-Inf-10) and National Quality Forum (NQF).6
Continue to: Overall, in the last 2 decades...
Overall, in the last 2 decades, the incidence of inadvertent perioperative hypothermia has decreased, mainly due to aggressive intraoperative management.7 In spite of this, studies have shown that perioperative hypothermia remains a significant problem in patients undergoing orthopedic procedures. In a recent community hospital study conducted by the National Association for Healthcare Quality that included 4124 orthopedic patients undergoing elective surgery, it was shown that, in spite of 99% compliance to the AMA-PCPI recommendation, 7.7% of orthopedic patients were found to be hypothermic.6
Management of hypothermia has long been an integral component of “damage control surgery” and resuscitation during polytrauma, which aims to aggressively minimize hypovolemic shock and limit the development of the lethal triad of hypothermia, coagulopathy, and acidosis.8 However, critical references to prevention and management of inadvertent perioperative hypothermia are lacking in the orthopedic literature on elective surgical procedures. This review aims to bridge this knowledge gap.
Unless otherwise specified, inadvertent perioperative hypothermia in this article refers to the core body temperature. In contrast, peripheral/limb hypothermia refers primarily to the effect of tourniquet application to the involved limb and the effect after deflation of the tourniquet on core body temperature.
RISK FACTORS
There are several measurable risk factors that can contribute to inadvertent perioperative hypothermia, which can be subdivided into 3 groups: patient-related risk factors, anesthesia-related risk factors, and procedure-related risk factors (Table 1).5,9-11 It is important to note that in any given patient a combination of 2 or more risk factors predisposes them to developing inadvertent perioperative hypothermia. Conceptualizing the etiology of inadvertent perioperative hypothermia in this way helps to plan a multipronged strategy to prevent it from occurring in the first place. Some of the important risk factors for inadvertent perioperative hypothermia are discussed below.
Table 1. Risk Factors for Perioperative Hypothermia
Patient-Related Risk Factors | Anesthesia-Related Risk Factors | Procedure-Specific Risk Factors |
|
|
|
To identify patient-related risk factors, researchers from the University of Louisville conducted a study including 2138 operative patients who became hypothermic after admission, of whom 27% underwent orthopedic and spine procedures.9 The patient-related risk factors identified were a high severity of illness on admission (odds ratio, 2.81; 95% CI, 2.28-3.47), presence of a neurological disorder such as Alzheimer’s disease (odds ratio, 1.71; 95% CI,1.06-2.78), male sex (odds ratio, 1.65; 95% CI, 1.36-2.01), age >65 years (odds ratio, 1.61; 95% CI, 1.33-1.96), recent weight loss (odds ratio, 1.60; 95% CI, 1.04-2.48), anemia (odds ratio, 1.49; 95% CI, 1.12-1.98), and chronic renal failure (odds ratio, 1.43; 95% CI, 1.07-1.92). Interestingly, diabetes mellitus without end-stage organ failure was not found to be a significant risk factor (odds ratio, 0.58; 95% CI, 0.44-0.75). It is also important to note that some of these risk factors identified to contribute to perioperative hypothermia are dependent on each other and others are independent of each other. For example, chronic renal failure and anemia are dependent risk factors. In contrast, age >65 years and low body mass index as risk factors of perioperative hypothermia are independent of each other.
Continue to: The second subgroup of risk factors...
The second subgroup of risk factors for perioperative hypothermia is related to anesthesia. The effect of general and regional anesthesia on perioperative core temperature is significantly different, both in terms of intraoperative thermoregulation and postoperative recovery.12 Intraoperatively, the core body temperature during the first 2 hours of general anesthesia decreases at a rate of 1.3°C per hour due to loss of thermoregulatory cutaneous and peripheral vasoconstrictive responses resulting in heat loss exceeding metabolic heat production. However, the core temperature remains virtually constant during the subsequent 3 hours due to the return of the thermoregulatory response, which causes cutaneous and peripheral vasoconstriction and increased metabolic heat production. Postoperative recovery from the hypothermia induced by general anesthesia is significantly faster than from that induced by regional anesthesia.13
The effect of regional hypothermia on core body temperature is more complex because it must be considered in addition to the effect of an associated procedure-related variable (ie, tourniquet application). If a tourniquet is not used during a surgery with regional anesthesia, a linear decrease in core temperature follows until recovery, due to increased blood flow from the loss of sympathetic peripheral vasoconstrictive response with resultant core-to-peripheral heat redistribution to the exposed operating limb. If a tourniquet is used during surgery with regional anesthesia, there will be no significant effect of the exposed operating limb on core temperature, as there is no blood flow between them. However, once the tourniquet is deflated, the core body temperature will be affected significantly as a result of core-to-peripheral distribution of heat to the operated limb with the return of blood flow. This fall in core body temperature after tourniquet deflation can be prevented by active forced-air warming initiated from the beginning of surgery.10 The extent and rate of development of peripheral/limb hypothermia during surgery (and its subsequent effect on core body temperature) depends on several factors, including the operating room ambient temperature, duration of tourniquet application, and temperature of the irrigation fluid. Postoperative recovery from the hypothermia induced by regional anesthesia takes longer than from that induced by general anesthesia because of the prolonged period of loss of vasoconstrictive response.
The third subgroup of risk factors associated with perioperative hypothermia is procedure related. Several procedure-specific risk factors for inadvertent perioperative hypothermia during arthroscopic surgery are identified, including prolonged operating time, low blood pressure during the procedure, and low temperature of the irrigation fluid.11 It is logical to extrapolate the importance of these risk factors to other orthopedic procedures which also require prolonged operating times, are performed under hypotension, or expose the patient to irrigation fluid that is at a low temperature. Understanding the importance of each of these procedure-related risk factors is the most important from the perspective of the orthopedic surgeon when compared to the rest of the subgroups of risk factors for inadvertent perioperative hypothermia as he/she is directly responsible for them.
The ambient operating room temperature has traditionally been considered a risk factor for inadvertent hypothermia in perioperative patients, but evidence is available to the contrary. The recommended ambient room temperature as per the clinical guideline published by the American Society of PeriAnesthesia Nurses (ASPAN) is 20°C to 24°C (68°F-75°F).14 The ambient temperature can have a significant effect on peripheral/limb hypothermia when operating on a limb with a tourniquet inflated, as the limb has no blood supply to distribute heat from the core to the periphery. However, the direct effect of ambient room temperature on the patient’s core body temperature is unlikely to be clinically significant if standard active warming interventions are implemented.15
COMPLICATIONS
The increased incidence of mortality due to inadvertent hypothermia in the perioperative period has already been discussed. Several other complications of inadvertent perioperative hypothermia include increased incidence of coagulopathy, acidosis, stroke, sepsis, pneumonia, myocardial infarction, surgical site infections, altered drug metabolism, and longer hospital stays.8,9,16-18 Hypothermia, coagulopathy, and acidosis have long been recognized as a lethal triad more commonly seen in polytrauma patients than in elective orthopedic surgery, as this occurs at extremes of temperature, usually <32°C. When compared with patients who did not develop perioperative hypothermia, patients who developed hypothermia during elective operations were shown to experience an overall doubled complication rate (13.9% vs 26.3%; P < .001) of which the incidence of stroke (1.0% vs 6.5%; P < .001), pneumonia (1.3% vs 5.1%; P < .001), and sepsis (2.6% vs 7.5%; P < .001) were much more likely than myocardial infarction (1.1% vs 3.3%; P = .01) and wound infection (3.3% vs 5.0%; P = .14).9
Continue to: Prevention...
PREVENTION
Prevention of perioperative hypothermia is a core measure to improve the outcome after ambulatory and fast-track orthopedic surgery and rehabilitation. Preventive strategies for perioperative hypothermia can be grouped into passive heat retention methods and active external warming methods (Table 2). Passive methods aim to maintain body temperature by decreasing the heat loss by radiation (eg, reflective blanket), conduction (eg, layered cotton blankets and padding the operating table), or convection (eg, heat and humidity exchanger in the breathing circuits) to the surrounding environment. Active patient heating methods aim to bring in heat from the source to the patient’s body using conduction (eg, Hot Dog® [Eden Augustine Temperature Management]) or convection (eg, Bair Hugger® [Arizant Healthcare]) techniques.
Table 2. Methods to Prevent Inadvertent Perioperative Hypothermia
Passive Heat-Retention Methods | Active External Warming Methods |
| Conduction techniques:
Convection techniques:
|
Active patient warming is superior to passive heat retention methods. A recent Cochrane study assessed the effects of standard care (ie, use of layered clothing and warm blankets, etc.) and addition of extra thermal insulation by reflective blankets or active forced air warming to standard care on the perioperative core body temperature.19 They concluded that there is no clear benefit of addition of extra thermal insulation by reflective blankets compared with standard care alone. Also, forced-air warming in addition to standard care appeared to maintain core temperature better than standard care alone, by between 0.5°C and 1°C, but the clinical importance of this difference could not be inferred, as none of the included studies in this meta-analysis documented major cardiovascular outcomes.
Several clinical guidelines have been developed by not-for-profit, government, and professional organizations aimed at prevention of perioperative hypothermia as primary or secondary outcome. A clinical guideline was published by ASPAN in 2001 for assessment, prevention, and intervention in unplanned perioperative hypothermia.14 Cost and time effectiveness of the ASPAN Hypothermia Guideline was published in 2008.20 The assessment guideline includes identification of risk factors, repeated pre-/intra-/postoperative temperature measurement, and repeated clinical evaluation of the patient’s status. The preventive guideline is to maintain an ambient temperature of 20°C to 24°C (68°F-75°F) and use appropriate passive patient warming methods pre-, intra-, and postoperatively. Intervention in the form of active patient heating is advised only if the patient develops hypothermia in spite of the above-mentioned standard preventive measures. But many orthopedic ambulatory surgery centers currently use active patient warming as both a preventive and an intervention strategy.
Active patient warming by conduction devices occurs by direct physical contact with the device, which is set at a higher temperature, whereas heat transfer from the convection device to the patient occurs by a physical medium such as forced air or circulating water that moves in between the device and the patient. Any recommendation for use of a specific technique of active patient warming (ie, by the use of a conduction device or a convection device) should only be given after comparing evidence on 3 critical aspects: efficacy, safety, and cost effectiveness.
The heating efficacy and core rewarming rates of conduction and convection devices have been compared in the literature. Full-body forced-air heating with the Bair Hugger® and full-body resistive polymer heating with the Hot Dog® in healthy volunteers were found to be similar.21 Also, in a randomized study conducted on 80 orthopedic patients undergoing surgery, resistive polymer warming performed as efficiently as forced-air warming in patients undergoing orthopedic surgery.22
Continue to: Secondly, the safety of convection...
Secondly, the safety of convection devices such as the Bair Hugger® has been under intense scrutiny based on the evidence that it disrupts the laminar airflow in the operating theater.23-26 This disruption in laminar air flow has been shown to cause emission of significant levels of airborne contaminants of size >0.3 μm (germ size).27 Isolates of Staphylococcus aureus, coagulase-negative Staphylococcus species, and methicillin-resistant Staphylococcus aureus were detected in 13.5%, 3.9%, and 1.9% of forced-air blowers, respectively.28 However, the clinical effect on the rate of deep joint infection due to the disruption of laminar air flow has been examined in only 1 study. McGovern and colleagues29 reported a significant increase in deep joint infection during a period when forced air warming was used compared to a period when conductive fabric warming was used (odds ratio, 3.8; P = .024) and recommended air-free warming by a conduction device over forced-air warming for orthopedic procedures. Unfortunately, the prophylactic antibiotic regimen was not kept constant during their study period. During an overlapping time frame during which they shifted from the use of a convection device (Bair Hugger®) to a conduction device (Hot Dog®), they also changed their antibiotic regimen from gentamicin 4.5 mg/kg intravenous (IV) to gentamicin 3 mg/kg IV plus teicoplanin 400 mg IV. This change in antibiotic regimen is a major confounding factor that calls into question the validity of the conclusions drawn by the authors.
Finally, the cost effectiveness of conduction and convection devices has never been studied. Hence, based on the current evidence, it is not possible to recommend a particular type of active patient-warming device.
CONCLUSION
Orthopedic surgeons should be aware that inadvertent perioperative hypothermia is a common phenomenon in perioperative patients. It must be recognized that the maintenance of perioperative normothermia during all major orthopedic surgical procedures is desirable, as inadvertent perioperative hypothermia is shown to be associated with increased mortality and systemic morbidity, such as stroke and sepsis. Compliance with the current clinical guidelines for assessment, prevention, and treatment of inadvertent perioperative hypothermia will minimize, if not eliminate, such risk. We recommend the following essential clinical guidelines to prevent inadvertent perioperative hypothermia (Table 3). Identification of patient-, anesthesia-, and procedure-related risk factors is an integral component of assessment of the risk of inadvertent perioperative hypothermia. In order to achieve full compliance with implementation of active patient warming during surgery, it is prudent to make active warming information a part of the surgical timeout checklist. Irrespective of the presence of risk factors, passive heat retention methods should be part of perioperative management of patients undergoing elective orthopedic surgery to prevent inadvertent perioperative hypothermia. In addition, there should be a minimum threshold to utilize active patient-warming techniques, especially in patients with inherent risk factors and surgeries that take >30 minutes of operating time, either under regional or general anesthesia. As there are concerns about safety issues with the use of convection devices, we believe a multicenter randomized controlled trial is warranted.
Table 3. Recommended Essential Clinical Guidelines for Prevention of Inadvertent Perioperative Hypothermia
|
ABSTRACT
Inadvertent perioperative hypothermia is a significant problem in patients undergoing either emergency or elective orthopedic surgery, and is associated with increased morbidity and mortality. Though in general the incidence of inadvertent perioperative hypothermia in postoperative recovery rooms has been decreasing over the last 2 decades, it still remains a significant risk in certain specialty practices, such as orthopedic surgery. This review article summarizes the currently available evidence on the incidence, risk factors, and complications of inadvertent perioperative hypothermia. Also, the effective preventive strategies in dealing with inadvertent perioperative hypothermia are reviewed and essential clinical guidelines to be followed are summarized.
Continue to: Inadvertent perioperative hypothermia...
Inadvertent perioperative hypothermia, defined as an involuntary drop in core body temperature to <35°C (95°F), is a condition associated with significant morbidity and mortality.1 This phenomenon has been reported in both emergency orthopedic admissions, such as fracture management, as well as in the elective setting such as arthroscopy, arthroplasty, and spine surgery.
In a study conducted in the United Kingdom including 781 elderly patients with a mean age of 80 years who presented with hip fractures, the 30-day mortality rate was 15.3% in patients who were admitted with a tympanic temperature of <36.5°C and only 5.1% in patients who maintained a tympanic temperature of 36.5°C to 37.5°C (odds ratio, 2.8; P > .0005).2 For an even better perspective, this analysis can be compared with the UK National Hip Fracture Database of 2013, which reported a 30-day mortality of 8.2% in patients who were admitted to the National Health Service with a diagnosis of hip fracture.3
Inadvertent perioperative hypothermia is also a common phenomenon during elective orthopedic hospital admissions. An Australian audit, which included 5050 postoperative patients, looked into the association between inadvertent perioperative hypothermia and mortality based on diagnostic criteria classifying mild hypothermia as a core temperature of <36°C and severe hypothermia as a core temperature of <35°C.4 The authors found that mild and severe hypothermia was experienced by 36% and 6% of patients, respectively. In-hospital mortality was 5.6% for normothermic patients, 8.9% for all hypothermic patients (P < .001), and 14.7% for severely hypothermic patients (P < .001). For a decrease of 1°C in core body temperature from <36°C to <35°C (but >34°C), there were higher odds of in-hospital mortality (odds ratio, 1.83; 95% confidence interval [CI], 1.20-2.60).
The physiologic response to hypothermia is to decrease heat loss by cutaneous and peripheral vasoconstriction and increase heat production by increasing the metabolic rate (eg, shivering and shifting to anaerobic metabolism). This response is blunted to a variable extent in perioperative patients for several reasons, including the effect of anesthetic drugs and old age.5
Maintenance of core body temperature >36°C is now a measured standard of perioperative care. A performance measure for perioperative temperature management was developed by the American Medical Association Physician Consortium for Performance Improvement (AMA-PCPI).6 To achieve this performance measure, mandatory documentation of use of active warming intraoperatively or a record of at least 1 body temperature ≥96.8°F (36°C) within 30 minutes immediately prior to and 15 minutes immediately after anesthesia end time is necessary. This performance measure is also endorsed by the Surgical Care Improvement Project (SCIP-Inf-10) and National Quality Forum (NQF).6
Continue to: Overall, in the last 2 decades...
Overall, in the last 2 decades, the incidence of inadvertent perioperative hypothermia has decreased, mainly due to aggressive intraoperative management.7 In spite of this, studies have shown that perioperative hypothermia remains a significant problem in patients undergoing orthopedic procedures. In a recent community hospital study conducted by the National Association for Healthcare Quality that included 4124 orthopedic patients undergoing elective surgery, it was shown that, in spite of 99% compliance to the AMA-PCPI recommendation, 7.7% of orthopedic patients were found to be hypothermic.6
Management of hypothermia has long been an integral component of “damage control surgery” and resuscitation during polytrauma, which aims to aggressively minimize hypovolemic shock and limit the development of the lethal triad of hypothermia, coagulopathy, and acidosis.8 However, critical references to prevention and management of inadvertent perioperative hypothermia are lacking in the orthopedic literature on elective surgical procedures. This review aims to bridge this knowledge gap.
Unless otherwise specified, inadvertent perioperative hypothermia in this article refers to the core body temperature. In contrast, peripheral/limb hypothermia refers primarily to the effect of tourniquet application to the involved limb and the effect after deflation of the tourniquet on core body temperature.
RISK FACTORS
There are several measurable risk factors that can contribute to inadvertent perioperative hypothermia, which can be subdivided into 3 groups: patient-related risk factors, anesthesia-related risk factors, and procedure-related risk factors (Table 1).5,9-11 It is important to note that in any given patient a combination of 2 or more risk factors predisposes them to developing inadvertent perioperative hypothermia. Conceptualizing the etiology of inadvertent perioperative hypothermia in this way helps to plan a multipronged strategy to prevent it from occurring in the first place. Some of the important risk factors for inadvertent perioperative hypothermia are discussed below.
Table 1. Risk Factors for Perioperative Hypothermia
Patient-Related Risk Factors | Anesthesia-Related Risk Factors | Procedure-Specific Risk Factors |
|
|
|
To identify patient-related risk factors, researchers from the University of Louisville conducted a study including 2138 operative patients who became hypothermic after admission, of whom 27% underwent orthopedic and spine procedures.9 The patient-related risk factors identified were a high severity of illness on admission (odds ratio, 2.81; 95% CI, 2.28-3.47), presence of a neurological disorder such as Alzheimer’s disease (odds ratio, 1.71; 95% CI,1.06-2.78), male sex (odds ratio, 1.65; 95% CI, 1.36-2.01), age >65 years (odds ratio, 1.61; 95% CI, 1.33-1.96), recent weight loss (odds ratio, 1.60; 95% CI, 1.04-2.48), anemia (odds ratio, 1.49; 95% CI, 1.12-1.98), and chronic renal failure (odds ratio, 1.43; 95% CI, 1.07-1.92). Interestingly, diabetes mellitus without end-stage organ failure was not found to be a significant risk factor (odds ratio, 0.58; 95% CI, 0.44-0.75). It is also important to note that some of these risk factors identified to contribute to perioperative hypothermia are dependent on each other and others are independent of each other. For example, chronic renal failure and anemia are dependent risk factors. In contrast, age >65 years and low body mass index as risk factors of perioperative hypothermia are independent of each other.
Continue to: The second subgroup of risk factors...
The second subgroup of risk factors for perioperative hypothermia is related to anesthesia. The effect of general and regional anesthesia on perioperative core temperature is significantly different, both in terms of intraoperative thermoregulation and postoperative recovery.12 Intraoperatively, the core body temperature during the first 2 hours of general anesthesia decreases at a rate of 1.3°C per hour due to loss of thermoregulatory cutaneous and peripheral vasoconstrictive responses resulting in heat loss exceeding metabolic heat production. However, the core temperature remains virtually constant during the subsequent 3 hours due to the return of the thermoregulatory response, which causes cutaneous and peripheral vasoconstriction and increased metabolic heat production. Postoperative recovery from the hypothermia induced by general anesthesia is significantly faster than from that induced by regional anesthesia.13
The effect of regional hypothermia on core body temperature is more complex because it must be considered in addition to the effect of an associated procedure-related variable (ie, tourniquet application). If a tourniquet is not used during a surgery with regional anesthesia, a linear decrease in core temperature follows until recovery, due to increased blood flow from the loss of sympathetic peripheral vasoconstrictive response with resultant core-to-peripheral heat redistribution to the exposed operating limb. If a tourniquet is used during surgery with regional anesthesia, there will be no significant effect of the exposed operating limb on core temperature, as there is no blood flow between them. However, once the tourniquet is deflated, the core body temperature will be affected significantly as a result of core-to-peripheral distribution of heat to the operated limb with the return of blood flow. This fall in core body temperature after tourniquet deflation can be prevented by active forced-air warming initiated from the beginning of surgery.10 The extent and rate of development of peripheral/limb hypothermia during surgery (and its subsequent effect on core body temperature) depends on several factors, including the operating room ambient temperature, duration of tourniquet application, and temperature of the irrigation fluid. Postoperative recovery from the hypothermia induced by regional anesthesia takes longer than from that induced by general anesthesia because of the prolonged period of loss of vasoconstrictive response.
The third subgroup of risk factors associated with perioperative hypothermia is procedure related. Several procedure-specific risk factors for inadvertent perioperative hypothermia during arthroscopic surgery are identified, including prolonged operating time, low blood pressure during the procedure, and low temperature of the irrigation fluid.11 It is logical to extrapolate the importance of these risk factors to other orthopedic procedures which also require prolonged operating times, are performed under hypotension, or expose the patient to irrigation fluid that is at a low temperature. Understanding the importance of each of these procedure-related risk factors is the most important from the perspective of the orthopedic surgeon when compared to the rest of the subgroups of risk factors for inadvertent perioperative hypothermia as he/she is directly responsible for them.
The ambient operating room temperature has traditionally been considered a risk factor for inadvertent hypothermia in perioperative patients, but evidence is available to the contrary. The recommended ambient room temperature as per the clinical guideline published by the American Society of PeriAnesthesia Nurses (ASPAN) is 20°C to 24°C (68°F-75°F).14 The ambient temperature can have a significant effect on peripheral/limb hypothermia when operating on a limb with a tourniquet inflated, as the limb has no blood supply to distribute heat from the core to the periphery. However, the direct effect of ambient room temperature on the patient’s core body temperature is unlikely to be clinically significant if standard active warming interventions are implemented.15
COMPLICATIONS
The increased incidence of mortality due to inadvertent hypothermia in the perioperative period has already been discussed. Several other complications of inadvertent perioperative hypothermia include increased incidence of coagulopathy, acidosis, stroke, sepsis, pneumonia, myocardial infarction, surgical site infections, altered drug metabolism, and longer hospital stays.8,9,16-18 Hypothermia, coagulopathy, and acidosis have long been recognized as a lethal triad more commonly seen in polytrauma patients than in elective orthopedic surgery, as this occurs at extremes of temperature, usually <32°C. When compared with patients who did not develop perioperative hypothermia, patients who developed hypothermia during elective operations were shown to experience an overall doubled complication rate (13.9% vs 26.3%; P < .001) of which the incidence of stroke (1.0% vs 6.5%; P < .001), pneumonia (1.3% vs 5.1%; P < .001), and sepsis (2.6% vs 7.5%; P < .001) were much more likely than myocardial infarction (1.1% vs 3.3%; P = .01) and wound infection (3.3% vs 5.0%; P = .14).9
Continue to: Prevention...
PREVENTION
Prevention of perioperative hypothermia is a core measure to improve the outcome after ambulatory and fast-track orthopedic surgery and rehabilitation. Preventive strategies for perioperative hypothermia can be grouped into passive heat retention methods and active external warming methods (Table 2). Passive methods aim to maintain body temperature by decreasing the heat loss by radiation (eg, reflective blanket), conduction (eg, layered cotton blankets and padding the operating table), or convection (eg, heat and humidity exchanger in the breathing circuits) to the surrounding environment. Active patient heating methods aim to bring in heat from the source to the patient’s body using conduction (eg, Hot Dog® [Eden Augustine Temperature Management]) or convection (eg, Bair Hugger® [Arizant Healthcare]) techniques.
Table 2. Methods to Prevent Inadvertent Perioperative Hypothermia
Passive Heat-Retention Methods | Active External Warming Methods |
| Conduction techniques:
Convection techniques:
|
Active patient warming is superior to passive heat retention methods. A recent Cochrane study assessed the effects of standard care (ie, use of layered clothing and warm blankets, etc.) and addition of extra thermal insulation by reflective blankets or active forced air warming to standard care on the perioperative core body temperature.19 They concluded that there is no clear benefit of addition of extra thermal insulation by reflective blankets compared with standard care alone. Also, forced-air warming in addition to standard care appeared to maintain core temperature better than standard care alone, by between 0.5°C and 1°C, but the clinical importance of this difference could not be inferred, as none of the included studies in this meta-analysis documented major cardiovascular outcomes.
Several clinical guidelines have been developed by not-for-profit, government, and professional organizations aimed at prevention of perioperative hypothermia as primary or secondary outcome. A clinical guideline was published by ASPAN in 2001 for assessment, prevention, and intervention in unplanned perioperative hypothermia.14 Cost and time effectiveness of the ASPAN Hypothermia Guideline was published in 2008.20 The assessment guideline includes identification of risk factors, repeated pre-/intra-/postoperative temperature measurement, and repeated clinical evaluation of the patient’s status. The preventive guideline is to maintain an ambient temperature of 20°C to 24°C (68°F-75°F) and use appropriate passive patient warming methods pre-, intra-, and postoperatively. Intervention in the form of active patient heating is advised only if the patient develops hypothermia in spite of the above-mentioned standard preventive measures. But many orthopedic ambulatory surgery centers currently use active patient warming as both a preventive and an intervention strategy.
Active patient warming by conduction devices occurs by direct physical contact with the device, which is set at a higher temperature, whereas heat transfer from the convection device to the patient occurs by a physical medium such as forced air or circulating water that moves in between the device and the patient. Any recommendation for use of a specific technique of active patient warming (ie, by the use of a conduction device or a convection device) should only be given after comparing evidence on 3 critical aspects: efficacy, safety, and cost effectiveness.
The heating efficacy and core rewarming rates of conduction and convection devices have been compared in the literature. Full-body forced-air heating with the Bair Hugger® and full-body resistive polymer heating with the Hot Dog® in healthy volunteers were found to be similar.21 Also, in a randomized study conducted on 80 orthopedic patients undergoing surgery, resistive polymer warming performed as efficiently as forced-air warming in patients undergoing orthopedic surgery.22
Continue to: Secondly, the safety of convection...
Secondly, the safety of convection devices such as the Bair Hugger® has been under intense scrutiny based on the evidence that it disrupts the laminar airflow in the operating theater.23-26 This disruption in laminar air flow has been shown to cause emission of significant levels of airborne contaminants of size >0.3 μm (germ size).27 Isolates of Staphylococcus aureus, coagulase-negative Staphylococcus species, and methicillin-resistant Staphylococcus aureus were detected in 13.5%, 3.9%, and 1.9% of forced-air blowers, respectively.28 However, the clinical effect on the rate of deep joint infection due to the disruption of laminar air flow has been examined in only 1 study. McGovern and colleagues29 reported a significant increase in deep joint infection during a period when forced air warming was used compared to a period when conductive fabric warming was used (odds ratio, 3.8; P = .024) and recommended air-free warming by a conduction device over forced-air warming for orthopedic procedures. Unfortunately, the prophylactic antibiotic regimen was not kept constant during their study period. During an overlapping time frame during which they shifted from the use of a convection device (Bair Hugger®) to a conduction device (Hot Dog®), they also changed their antibiotic regimen from gentamicin 4.5 mg/kg intravenous (IV) to gentamicin 3 mg/kg IV plus teicoplanin 400 mg IV. This change in antibiotic regimen is a major confounding factor that calls into question the validity of the conclusions drawn by the authors.
Finally, the cost effectiveness of conduction and convection devices has never been studied. Hence, based on the current evidence, it is not possible to recommend a particular type of active patient-warming device.
CONCLUSION
Orthopedic surgeons should be aware that inadvertent perioperative hypothermia is a common phenomenon in perioperative patients. It must be recognized that the maintenance of perioperative normothermia during all major orthopedic surgical procedures is desirable, as inadvertent perioperative hypothermia is shown to be associated with increased mortality and systemic morbidity, such as stroke and sepsis. Compliance with the current clinical guidelines for assessment, prevention, and treatment of inadvertent perioperative hypothermia will minimize, if not eliminate, such risk. We recommend the following essential clinical guidelines to prevent inadvertent perioperative hypothermia (Table 3). Identification of patient-, anesthesia-, and procedure-related risk factors is an integral component of assessment of the risk of inadvertent perioperative hypothermia. In order to achieve full compliance with implementation of active patient warming during surgery, it is prudent to make active warming information a part of the surgical timeout checklist. Irrespective of the presence of risk factors, passive heat retention methods should be part of perioperative management of patients undergoing elective orthopedic surgery to prevent inadvertent perioperative hypothermia. In addition, there should be a minimum threshold to utilize active patient-warming techniques, especially in patients with inherent risk factors and surgeries that take >30 minutes of operating time, either under regional or general anesthesia. As there are concerns about safety issues with the use of convection devices, we believe a multicenter randomized controlled trial is warranted.
Table 3. Recommended Essential Clinical Guidelines for Prevention of Inadvertent Perioperative Hypothermia
|
- Brown DJ, Brugger H, Boyd J, Paal P. Accidental Hypothermia. N Engl J Med. 2012;367(20):1930-1938. doi:10.1056/NEJMra1114208.
- Uzoigwe CE, Khan A, Smith RP, et al. Hypothermia and low body temperature are common and associated with high mortality in hip fracture patients. Hip Int. 2014; 24(3):237-242. doi:10.5301/hipint.5000124.
- Johansen A, Wakeman R, Boulton C, Plant F, Roberts J, Williams A. National Hip Fracture Database: National Report 2013. London, UK: National Hip Fracture Database, Royal College of Physicians; 2013.
- Karalapillai D, Story DA, Calzavacca, Licari E, Liu YL, Hart GK. Inadvertent hypothermia and mortality in postoperative intensive care patients: retrospective audit of 5050 patients. Anaesthesia. 2009;64(9):968-972. doi:10.1111/j.1365-2044.2009.05989.x.
- Horosz B, Malec-Milewska M. Inadvertent intraoperative hypothermia. Anaesthesiol Intensive Ther. 2013;45(1):38-43. doi:10.5603/AIT.2013.0009.
- Steelman VM, Perkhounkova YS, Lemke JH. The gap between compliance with the quality performance measure "perioperative temperature management” and normothermia. J Healthc Qual. 2014;37(6):333-341. doi:10.1111/jhq.12063.
- National Institute for Health and Clinical Excellence. Inadvertent Perioperative Hypothermia: The Management of Inadvertent Perioperative Hypothermia in Adults. London, UK: National Institute for Health and Clinical Excellence; 2008.
- Carlino W. Damage control resuscitation from major haemorrhage in polytrauma. Eur J Orthop Surg Traumatol. 2014;24(2):137-141. doi:10.1007/s00590-013-1172-7.
- Billeter AT, Hohmann SF, Druen D, Cannon R, Polk HC Jr. Unintentional perioperative hypothermia is associated with severe complications and high mortality in elective operations. Surgery. 2014;156(5):1245-1252. doi:10.1016/j.surg.2014.04.024.
- Kim YS, Jeon YS, Lee JA, et al. Intra-operative warming with a forced-air warmer in preventing hypothermia after tourniquet deflation in elderly patients. J Int Med Res. 2009;37(5):1457-1464. doi:10.1177/147323000903700521.
- Parodi D, Tobar C, Valderrama J, et al. Hip arthroscopy and hypothermia. Arthroscopy. 2012;28(7):924-928. doi:10.1016/j.arthro.2011.12.012.
- Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology. 1995;83(3):491-499.
- Vaughan MS, Vaughan RW, Cork RC. Postoperative hypothermia in adults: relationship of age, anesthesia, and shivering to rewarming. Anesth Analg. 1981;60(10):746-751.
- American Society of PeriAnesthesia Nurses. Clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):305-314.
- Inaba K, Berg R, Barmparas G, et al. Prospective evaluation of ambient operating room temperature on the core temperature of injured patients undergoing emergent surgery. J Trauma Acute Care Surg. 2012;73(6):1478-1483. doi:10.1097/TA.0b013e3182781db3.
- Barie PS. Surgical site infections: epidemiology and prevention. Surg Infect (Larchmt). 2002;3 Suppl 1:S9-S21. doi:10.1089/sur.2002.3.s1-9.
- Jeran L. Patient temperature: an introduction to the clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):303-304.
- Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334(19):1209-1215.
- Alderson P, Campbell G, Smith AF, Warttig S, Nicholson A, Lewis SR. Thermal insulation for preventing inadvertent perioperative hypothermia. Cochrane Database Syst Rev. 2014;6:CD009908. doi:10.1002/14651858.CD009908.pub2.
- Berry D, Wick C, Magons P. A clinical evaluation of the cost and time effectiveness of the ASPAN Hypothermia Guideline. J Perianesth Nurs. 2008;23(1):24-35. doi:10.1016/j.jopan.2007.09.010.
- Kimberger O, Held C, Stadelmann K et al. Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers. Anesth Analg. 2008;107(5):1621-1626. doi:10.1213/ane.0b013e3181845502.
- Brandt S, Oguz R, Hüttner H, et al. Resistive-polymer versus forced-air warming: comparable efficacy in orthopedic patients. Anesth Analg. 2010;110(3):834-838. doi:10.1213/ANE.0b013e3181cb3f5f.
- Legg AJ, Hammer AJ. Forced-air patient warming blankets disrupt unidirectional airflow. Bone Joint J. 2013;95-B(3):407-410. doi:10.1302/0301-620X.95B3.29121.
- Dasari KB, Albrecht M, Harper M. Effect of forced-air warming on the performance of operating theatre laminar flow ventilation. Anaesthesia. 2012;67(3):244-249. doi:10.1111/j.1365-2044.2011.06983.x.
- Belani KG, Albrecht M, McGovern PD, Reed M, Nachtsheim C. Patient warming excess heat: the effects on orthopedic operating room ventilation performance. Anesth Analg. 2013;117(2):406-411. doi:10.1213/ANE.0b013e31825f81e2.
- Legg AJ, Cannon T, Hammer AJ. Do forced air patient-warming devices disrupt unidirectional downward airflow? J Bone Joint Surg Br. 2012;94(2):254-256. doi:10.1302/0301-620X.94B2.27562.
- Albrecht M, Gaithier RL, Belani K, Litchy M, Leaper D. Forced-air warming blowers: An evaluation of filtration adequacy and airborne contamination emissions in the operating room. Am J Infect Control. 2011;39(4):321-328. doi:10.1016/j.ajic.2010.06.011.
- Reed M, Kimberger O, McGovern PD, Albrecht MC. Forced-air warming design: evaluation of intake filtration, internal microbial buildup, and airborne-contamination emissions. AANA J. 2013;81(4):275-280.
- McGovern PD, Albercht M, Belani KG, et al. Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics. J Bone Joint Surg Br.2011;93(11):1537-1544. doi:10.1302/0301-620X.93B11.27124.
- Brown DJ, Brugger H, Boyd J, Paal P. Accidental Hypothermia. N Engl J Med. 2012;367(20):1930-1938. doi:10.1056/NEJMra1114208.
- Uzoigwe CE, Khan A, Smith RP, et al. Hypothermia and low body temperature are common and associated with high mortality in hip fracture patients. Hip Int. 2014; 24(3):237-242. doi:10.5301/hipint.5000124.
- Johansen A, Wakeman R, Boulton C, Plant F, Roberts J, Williams A. National Hip Fracture Database: National Report 2013. London, UK: National Hip Fracture Database, Royal College of Physicians; 2013.
- Karalapillai D, Story DA, Calzavacca, Licari E, Liu YL, Hart GK. Inadvertent hypothermia and mortality in postoperative intensive care patients: retrospective audit of 5050 patients. Anaesthesia. 2009;64(9):968-972. doi:10.1111/j.1365-2044.2009.05989.x.
- Horosz B, Malec-Milewska M. Inadvertent intraoperative hypothermia. Anaesthesiol Intensive Ther. 2013;45(1):38-43. doi:10.5603/AIT.2013.0009.
- Steelman VM, Perkhounkova YS, Lemke JH. The gap between compliance with the quality performance measure "perioperative temperature management” and normothermia. J Healthc Qual. 2014;37(6):333-341. doi:10.1111/jhq.12063.
- National Institute for Health and Clinical Excellence. Inadvertent Perioperative Hypothermia: The Management of Inadvertent Perioperative Hypothermia in Adults. London, UK: National Institute for Health and Clinical Excellence; 2008.
- Carlino W. Damage control resuscitation from major haemorrhage in polytrauma. Eur J Orthop Surg Traumatol. 2014;24(2):137-141. doi:10.1007/s00590-013-1172-7.
- Billeter AT, Hohmann SF, Druen D, Cannon R, Polk HC Jr. Unintentional perioperative hypothermia is associated with severe complications and high mortality in elective operations. Surgery. 2014;156(5):1245-1252. doi:10.1016/j.surg.2014.04.024.
- Kim YS, Jeon YS, Lee JA, et al. Intra-operative warming with a forced-air warmer in preventing hypothermia after tourniquet deflation in elderly patients. J Int Med Res. 2009;37(5):1457-1464. doi:10.1177/147323000903700521.
- Parodi D, Tobar C, Valderrama J, et al. Hip arthroscopy and hypothermia. Arthroscopy. 2012;28(7):924-928. doi:10.1016/j.arthro.2011.12.012.
- Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology. 1995;83(3):491-499.
- Vaughan MS, Vaughan RW, Cork RC. Postoperative hypothermia in adults: relationship of age, anesthesia, and shivering to rewarming. Anesth Analg. 1981;60(10):746-751.
- American Society of PeriAnesthesia Nurses. Clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):305-314.
- Inaba K, Berg R, Barmparas G, et al. Prospective evaluation of ambient operating room temperature on the core temperature of injured patients undergoing emergent surgery. J Trauma Acute Care Surg. 2012;73(6):1478-1483. doi:10.1097/TA.0b013e3182781db3.
- Barie PS. Surgical site infections: epidemiology and prevention. Surg Infect (Larchmt). 2002;3 Suppl 1:S9-S21. doi:10.1089/sur.2002.3.s1-9.
- Jeran L. Patient temperature: an introduction to the clinical guideline for the prevention of unplanned perioperative hypothermia. J Perianesth Nurs. 2001;16(5):303-304.
- Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334(19):1209-1215.
- Alderson P, Campbell G, Smith AF, Warttig S, Nicholson A, Lewis SR. Thermal insulation for preventing inadvertent perioperative hypothermia. Cochrane Database Syst Rev. 2014;6:CD009908. doi:10.1002/14651858.CD009908.pub2.
- Berry D, Wick C, Magons P. A clinical evaluation of the cost and time effectiveness of the ASPAN Hypothermia Guideline. J Perianesth Nurs. 2008;23(1):24-35. doi:10.1016/j.jopan.2007.09.010.
- Kimberger O, Held C, Stadelmann K et al. Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers. Anesth Analg. 2008;107(5):1621-1626. doi:10.1213/ane.0b013e3181845502.
- Brandt S, Oguz R, Hüttner H, et al. Resistive-polymer versus forced-air warming: comparable efficacy in orthopedic patients. Anesth Analg. 2010;110(3):834-838. doi:10.1213/ANE.0b013e3181cb3f5f.
- Legg AJ, Hammer AJ. Forced-air patient warming blankets disrupt unidirectional airflow. Bone Joint J. 2013;95-B(3):407-410. doi:10.1302/0301-620X.95B3.29121.
- Dasari KB, Albrecht M, Harper M. Effect of forced-air warming on the performance of operating theatre laminar flow ventilation. Anaesthesia. 2012;67(3):244-249. doi:10.1111/j.1365-2044.2011.06983.x.
- Belani KG, Albrecht M, McGovern PD, Reed M, Nachtsheim C. Patient warming excess heat: the effects on orthopedic operating room ventilation performance. Anesth Analg. 2013;117(2):406-411. doi:10.1213/ANE.0b013e31825f81e2.
- Legg AJ, Cannon T, Hammer AJ. Do forced air patient-warming devices disrupt unidirectional downward airflow? J Bone Joint Surg Br. 2012;94(2):254-256. doi:10.1302/0301-620X.94B2.27562.
- Albrecht M, Gaithier RL, Belani K, Litchy M, Leaper D. Forced-air warming blowers: An evaluation of filtration adequacy and airborne contamination emissions in the operating room. Am J Infect Control. 2011;39(4):321-328. doi:10.1016/j.ajic.2010.06.011.
- Reed M, Kimberger O, McGovern PD, Albrecht MC. Forced-air warming design: evaluation of intake filtration, internal microbial buildup, and airborne-contamination emissions. AANA J. 2013;81(4):275-280.
- McGovern PD, Albercht M, Belani KG, et al. Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics. J Bone Joint Surg Br.2011;93(11):1537-1544. doi:10.1302/0301-620X.93B11.27124.
TAKE-HOME POINTS
- Inadvertent perioperative hypothermia, defined as an involuntary drop in core body temperature to <35°C (95°F), is a condition associated with significant morbidity and mortality.
- Maintenance of core body temperature >36°C is now a measured standard of perioperative care.
- Overall, in the last 2 decades, the incidence of inadvertent perioperative hypothermia has decreased, mainly due to aggressive intraoperative management.
- Active patient warming by conduction devices occurs by direct physical contact with the device, which is set at a higher temperature, whereas heat transfer from the convection device to the patient occurs by a physical medium such as forced air or circulating water that moves in between the device and the patient.
- Active patient warming is superior to passive heat retention methods.
SAMHSA Releases Money for Opioid Treatment
The Targeted Capacity Expansion: Medication Assisted Treatment-Prescription Drug Opioid Addiction grant program will expand access to treatment and recovery support services in states, tribes, and tribal organizations with the highest per-capita rates of primary treatment admissions for heroin and prescription opioids. The funding includes the areas with the “most dramatic increases” for heroin and prescription opioids, as identified by SAMHSA’s 2015 Treatment Episode Data Set.
“We know medication-assisted treatment is an effective, essential tool in fighting the opioid crisis,” said HHS Secretary Alex Azar, “and HHS will continue working to expand access to it.”
The Targeted Capacity Expansion: Medication Assisted Treatment-Prescription Drug Opioid Addiction grant program will expand access to treatment and recovery support services in states, tribes, and tribal organizations with the highest per-capita rates of primary treatment admissions for heroin and prescription opioids. The funding includes the areas with the “most dramatic increases” for heroin and prescription opioids, as identified by SAMHSA’s 2015 Treatment Episode Data Set.
“We know medication-assisted treatment is an effective, essential tool in fighting the opioid crisis,” said HHS Secretary Alex Azar, “and HHS will continue working to expand access to it.”
The Targeted Capacity Expansion: Medication Assisted Treatment-Prescription Drug Opioid Addiction grant program will expand access to treatment and recovery support services in states, tribes, and tribal organizations with the highest per-capita rates of primary treatment admissions for heroin and prescription opioids. The funding includes the areas with the “most dramatic increases” for heroin and prescription opioids, as identified by SAMHSA’s 2015 Treatment Episode Data Set.
“We know medication-assisted treatment is an effective, essential tool in fighting the opioid crisis,” said HHS Secretary Alex Azar, “and HHS will continue working to expand access to it.”
Federal Health Care Data Trends: Cardiovascular Diseases
Cardiovascular disease remains a significant cause of morbidity and mortality. According to the American Heart Association, in the US, every 40 seconds someone experiences a stroke, another person has a heart attack, and a third person dies of cardiovascular disease.1 More than 92 million American adults have some form of cardiovascular disease or poststroke symptoms, and the costs are well above $300 billion.1
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Cardiovascular disease remains a significant cause of morbidity and mortality. According to the American Heart Association, in the US, every 40 seconds someone experiences a stroke, another person has a heart attack, and a third person dies of cardiovascular disease.1 More than 92 million American adults have some form of cardiovascular disease or poststroke symptoms, and the costs are well above $300 billion.1
Click here to continue reading.
Cardiovascular disease remains a significant cause of morbidity and mortality. According to the American Heart Association, in the US, every 40 seconds someone experiences a stroke, another person has a heart attack, and a third person dies of cardiovascular disease.1 More than 92 million American adults have some form of cardiovascular disease or poststroke symptoms, and the costs are well above $300 billion.1
Click here to continue reading.
Study links gut bacteria and TRALI
A new study has revealed a previously unknown link between gastrointestinal flora and transfusion-related acute lung injury (TRALI).
“We observed that the composition of the gastrointestinal flora drives the pathogenic immune response in the lungs during TRALI,” said Rick Kapur, PhD, of Lund University in Lund, Sweden.
Dr Kapur and his colleagues described this discovery in Blood Advances.
The researchers compared 2 groups of mice. One group was kept in a strictly sterile environment, allowing the gastrointestinal flora to be minimally affected by external factors. The other group was raised in a normal, less sterile environment.
“We saw that the mice kept in a more sterile environment were resistant to TRALI development, while the less sterile-raised mice developed severe TRALI,” said study author John W. Semple, PhD, of Lund University.
The composition of the gastrointestinal flora was significantly different between the 2 groups of mice, as determined by genetic sequencing of stool.
When the researchers wiped out the gastrointestinal flora with several types of antibiotics, they found that mice in the less sterile environment did not develop TRALI.
The researchers also transplanted stool from mice that developed TRALI into TRALI-resistant mice. After the stool transplant, the resistant mice were also able to develop TRALI, which confirmed the link between the composition of the gastrointestinal flora and the onset of TRALI.
The researchers still need to clarify which specific gut bacteria are directly involved, but the knowledge that intestinal bacteria may affect the lungs could facilitate diagnostics and the development of potential new drugs.
The ability to easily assess the risk for TRALI via analysis of gastrointestinal flora is equally important, according to the researchers.
“Knowing the composition of the gastrointestinal flora of people who will receive blood transfusions, an analysis which can be easily performed today, would allow you to assess who may be at increased risk for developing TRALI,” Dr Kapur said.
“The TRALI model in mice is very similar to the condition in humans, and the next step will be to validate these findings in humans,” Dr Semple said. “It’s not often that these types of findings in mice can lead directly to clinical studies in humans, but that will be our aim.”
A new study has revealed a previously unknown link between gastrointestinal flora and transfusion-related acute lung injury (TRALI).
“We observed that the composition of the gastrointestinal flora drives the pathogenic immune response in the lungs during TRALI,” said Rick Kapur, PhD, of Lund University in Lund, Sweden.
Dr Kapur and his colleagues described this discovery in Blood Advances.
The researchers compared 2 groups of mice. One group was kept in a strictly sterile environment, allowing the gastrointestinal flora to be minimally affected by external factors. The other group was raised in a normal, less sterile environment.
“We saw that the mice kept in a more sterile environment were resistant to TRALI development, while the less sterile-raised mice developed severe TRALI,” said study author John W. Semple, PhD, of Lund University.
The composition of the gastrointestinal flora was significantly different between the 2 groups of mice, as determined by genetic sequencing of stool.
When the researchers wiped out the gastrointestinal flora with several types of antibiotics, they found that mice in the less sterile environment did not develop TRALI.
The researchers also transplanted stool from mice that developed TRALI into TRALI-resistant mice. After the stool transplant, the resistant mice were also able to develop TRALI, which confirmed the link between the composition of the gastrointestinal flora and the onset of TRALI.
The researchers still need to clarify which specific gut bacteria are directly involved, but the knowledge that intestinal bacteria may affect the lungs could facilitate diagnostics and the development of potential new drugs.
The ability to easily assess the risk for TRALI via analysis of gastrointestinal flora is equally important, according to the researchers.
“Knowing the composition of the gastrointestinal flora of people who will receive blood transfusions, an analysis which can be easily performed today, would allow you to assess who may be at increased risk for developing TRALI,” Dr Kapur said.
“The TRALI model in mice is very similar to the condition in humans, and the next step will be to validate these findings in humans,” Dr Semple said. “It’s not often that these types of findings in mice can lead directly to clinical studies in humans, but that will be our aim.”
A new study has revealed a previously unknown link between gastrointestinal flora and transfusion-related acute lung injury (TRALI).
“We observed that the composition of the gastrointestinal flora drives the pathogenic immune response in the lungs during TRALI,” said Rick Kapur, PhD, of Lund University in Lund, Sweden.
Dr Kapur and his colleagues described this discovery in Blood Advances.
The researchers compared 2 groups of mice. One group was kept in a strictly sterile environment, allowing the gastrointestinal flora to be minimally affected by external factors. The other group was raised in a normal, less sterile environment.
“We saw that the mice kept in a more sterile environment were resistant to TRALI development, while the less sterile-raised mice developed severe TRALI,” said study author John W. Semple, PhD, of Lund University.
The composition of the gastrointestinal flora was significantly different between the 2 groups of mice, as determined by genetic sequencing of stool.
When the researchers wiped out the gastrointestinal flora with several types of antibiotics, they found that mice in the less sterile environment did not develop TRALI.
The researchers also transplanted stool from mice that developed TRALI into TRALI-resistant mice. After the stool transplant, the resistant mice were also able to develop TRALI, which confirmed the link between the composition of the gastrointestinal flora and the onset of TRALI.
The researchers still need to clarify which specific gut bacteria are directly involved, but the knowledge that intestinal bacteria may affect the lungs could facilitate diagnostics and the development of potential new drugs.
The ability to easily assess the risk for TRALI via analysis of gastrointestinal flora is equally important, according to the researchers.
“Knowing the composition of the gastrointestinal flora of people who will receive blood transfusions, an analysis which can be easily performed today, would allow you to assess who may be at increased risk for developing TRALI,” Dr Kapur said.
“The TRALI model in mice is very similar to the condition in humans, and the next step will be to validate these findings in humans,” Dr Semple said. “It’s not often that these types of findings in mice can lead directly to clinical studies in humans, but that will be our aim.”
Protein could be target for MLL-rearranged AML
Preclinical research has revealed a potential therapeutic target for MLL-rearranged acute myeloid leukemia (AML).
The target—F-box protein S-phase kinase-associated protein 2 (Skp2)—degrades another protein called p27Kip1 that is important to the formation of healthy blood cells.
This finding was published in the Journal of Experimental Medicine.
“Our work provides a complete mechanistic look into the function of genetic and molecular programs driving this leukemia, and it exploits these processes to identify actionable therapeutic targets,’’ said study author H. Leighton Grimes, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio.
For this work, Dr Grimes and his colleagues performed biochemical analyses of cells from AML patients. This gave the researchers comprehensive information about the targets and functions of the miR-196 molecular signaling pathway.
The team inserted mimics of miR-196 into MLL-AF9 leukemia cells to incorporate them into the cellular machinery. The group then lysed the cells for analyses, which revealed molecular targets of miR-196 in the leukemia cells.
Next, the researchers screened AML cells in mice for miR-196 targets. These experiments showed that certain microRNA targets are more important than others in the maintenance and spread of leukemia stem cells (LSCs).
Computer-assisted analysis of the Molecular Signature Database (a shared multi-institutional resource) allowed the researchers to identify sets of genes that show up in high numbers in MLL-AF9 leukemia.
Additional biochemical testing revealed that miR-196 directly targets and inhibits Cdkn1b/p27Kip1, which controls molecular programming in LSCs that allows them to maintain aggressive MLL-AF9 leukemia.
When miR-196 targets Cdkn1b/p27Kip1, it accelerates MLL-AF9 progression by abnormally linking stem cell activity with the growth of leukemia cells.
With the data suggesting that elevation of p27Kip1 protein levels may be therapeutic to AML patients, the researchers investigated a related molecular pathway that also regulates p27Kip1.
This investigation yielded the treatment target Skp2, which degrades the p27 protein and lowers its expression.
The researchers tested an experimental Skp2 inhibitor, SLZ P1041, on human AML cell lines and found the drug killed AML cells in a dose-dependent manner.
The team also tested SLZ P1041 in combination with other inhibitors—IBET-151, palbociclib, and MI-1. The most consistent synergies were with the combination of SLZ P1041 and MI-1, an inhibitor of the interaction between Menin and MLL.
“We still have extensive additional testing to conduct in laboratory animal models of AML before knowing if [targeting Skp2] will translate to patient care,” Dr Grimes said.
Preclinical research has revealed a potential therapeutic target for MLL-rearranged acute myeloid leukemia (AML).
The target—F-box protein S-phase kinase-associated protein 2 (Skp2)—degrades another protein called p27Kip1 that is important to the formation of healthy blood cells.
This finding was published in the Journal of Experimental Medicine.
“Our work provides a complete mechanistic look into the function of genetic and molecular programs driving this leukemia, and it exploits these processes to identify actionable therapeutic targets,’’ said study author H. Leighton Grimes, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio.
For this work, Dr Grimes and his colleagues performed biochemical analyses of cells from AML patients. This gave the researchers comprehensive information about the targets and functions of the miR-196 molecular signaling pathway.
The team inserted mimics of miR-196 into MLL-AF9 leukemia cells to incorporate them into the cellular machinery. The group then lysed the cells for analyses, which revealed molecular targets of miR-196 in the leukemia cells.
Next, the researchers screened AML cells in mice for miR-196 targets. These experiments showed that certain microRNA targets are more important than others in the maintenance and spread of leukemia stem cells (LSCs).
Computer-assisted analysis of the Molecular Signature Database (a shared multi-institutional resource) allowed the researchers to identify sets of genes that show up in high numbers in MLL-AF9 leukemia.
Additional biochemical testing revealed that miR-196 directly targets and inhibits Cdkn1b/p27Kip1, which controls molecular programming in LSCs that allows them to maintain aggressive MLL-AF9 leukemia.
When miR-196 targets Cdkn1b/p27Kip1, it accelerates MLL-AF9 progression by abnormally linking stem cell activity with the growth of leukemia cells.
With the data suggesting that elevation of p27Kip1 protein levels may be therapeutic to AML patients, the researchers investigated a related molecular pathway that also regulates p27Kip1.
This investigation yielded the treatment target Skp2, which degrades the p27 protein and lowers its expression.
The researchers tested an experimental Skp2 inhibitor, SLZ P1041, on human AML cell lines and found the drug killed AML cells in a dose-dependent manner.
The team also tested SLZ P1041 in combination with other inhibitors—IBET-151, palbociclib, and MI-1. The most consistent synergies were with the combination of SLZ P1041 and MI-1, an inhibitor of the interaction between Menin and MLL.
“We still have extensive additional testing to conduct in laboratory animal models of AML before knowing if [targeting Skp2] will translate to patient care,” Dr Grimes said.
Preclinical research has revealed a potential therapeutic target for MLL-rearranged acute myeloid leukemia (AML).
The target—F-box protein S-phase kinase-associated protein 2 (Skp2)—degrades another protein called p27Kip1 that is important to the formation of healthy blood cells.
This finding was published in the Journal of Experimental Medicine.
“Our work provides a complete mechanistic look into the function of genetic and molecular programs driving this leukemia, and it exploits these processes to identify actionable therapeutic targets,’’ said study author H. Leighton Grimes, PhD, of Cincinnati Children’s Hospital Medical Center in Ohio.
For this work, Dr Grimes and his colleagues performed biochemical analyses of cells from AML patients. This gave the researchers comprehensive information about the targets and functions of the miR-196 molecular signaling pathway.
The team inserted mimics of miR-196 into MLL-AF9 leukemia cells to incorporate them into the cellular machinery. The group then lysed the cells for analyses, which revealed molecular targets of miR-196 in the leukemia cells.
Next, the researchers screened AML cells in mice for miR-196 targets. These experiments showed that certain microRNA targets are more important than others in the maintenance and spread of leukemia stem cells (LSCs).
Computer-assisted analysis of the Molecular Signature Database (a shared multi-institutional resource) allowed the researchers to identify sets of genes that show up in high numbers in MLL-AF9 leukemia.
Additional biochemical testing revealed that miR-196 directly targets and inhibits Cdkn1b/p27Kip1, which controls molecular programming in LSCs that allows them to maintain aggressive MLL-AF9 leukemia.
When miR-196 targets Cdkn1b/p27Kip1, it accelerates MLL-AF9 progression by abnormally linking stem cell activity with the growth of leukemia cells.
With the data suggesting that elevation of p27Kip1 protein levels may be therapeutic to AML patients, the researchers investigated a related molecular pathway that also regulates p27Kip1.
This investigation yielded the treatment target Skp2, which degrades the p27 protein and lowers its expression.
The researchers tested an experimental Skp2 inhibitor, SLZ P1041, on human AML cell lines and found the drug killed AML cells in a dose-dependent manner.
The team also tested SLZ P1041 in combination with other inhibitors—IBET-151, palbociclib, and MI-1. The most consistent synergies were with the combination of SLZ P1041 and MI-1, an inhibitor of the interaction between Menin and MLL.
“We still have extensive additional testing to conduct in laboratory animal models of AML before knowing if [targeting Skp2] will translate to patient care,” Dr Grimes said.
FDA releases guidance docs on gene therapy
The US Food and Drug Administration (FDA) has released several draft guidance documents on gene therapy.
Three are disease-specific guidances—for hemophilia, rare diseases, and retinal disorders—and 3 are guidances on manufacturing gene therapies.
These 6 documents are intended to serve as the building blocks of a modern, comprehensive framework for advancing the field of gene therapy, according to FDA Commissioner Scott Gottlieb, MD.
He said the documents are being issued in draft form so the FDA can solicit public input on these new policies. As with all draft guidances, all comments received will be considered before the FDA finalizes the documents.
Disease-specific guidances
The Human Gene Therapy for Rare Diseases Draft Guidance and the Human Gene Therapy for Retinal Disorders Draft Guidance include considerations for product development, preclinical research, clinical trials, expedited programs, and communication with the FDA.
The Human Gene Therapy for Hemophilia Draft Guidance covers the same topics but also includes considerations for measuring factor VIII and factor IX activity.
The draft guidance for rare diseases encompasses diseases affecting fewer than 200,000 people in the US.
Manufacturing guidances
The 3 remaining draft guidances are actually updates to existing guidances that address manufacturing issues related to gene therapy.
The first updated draft guidance, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), provides sponsors with recommendations on how to provide sufficient CMC information to ensure safety, identity, quality, purity, and strength/potency of investigational gene therapy products. This guidance applies to gene therapies alone and products that contain a gene therapy in combination with a drug or device.
The second draft guidance, Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus (RCR) during Product Manufacture and Patient Follow-up, provides recommendations regarding the proper testing for RCR during the manufacture of retroviral vector-based gene therapy products, as well as during the follow-up monitoring of patients who have received retroviral vector-based gene therapy products.
The third draft guidance, Long Term Follow-Up (LTFU) After Administration of Human Gene Therapy Products, provides recommendations regarding the design of LTFU observational studies for the collection of data on delayed adverse events after gene therapy.
Once finalized, these draft guidances will replace previous guidances issued by the FDA in April 2008 (CMC) and November 2006 (RCR and LTFU).
The US Food and Drug Administration (FDA) has released several draft guidance documents on gene therapy.
Three are disease-specific guidances—for hemophilia, rare diseases, and retinal disorders—and 3 are guidances on manufacturing gene therapies.
These 6 documents are intended to serve as the building blocks of a modern, comprehensive framework for advancing the field of gene therapy, according to FDA Commissioner Scott Gottlieb, MD.
He said the documents are being issued in draft form so the FDA can solicit public input on these new policies. As with all draft guidances, all comments received will be considered before the FDA finalizes the documents.
Disease-specific guidances
The Human Gene Therapy for Rare Diseases Draft Guidance and the Human Gene Therapy for Retinal Disorders Draft Guidance include considerations for product development, preclinical research, clinical trials, expedited programs, and communication with the FDA.
The Human Gene Therapy for Hemophilia Draft Guidance covers the same topics but also includes considerations for measuring factor VIII and factor IX activity.
The draft guidance for rare diseases encompasses diseases affecting fewer than 200,000 people in the US.
Manufacturing guidances
The 3 remaining draft guidances are actually updates to existing guidances that address manufacturing issues related to gene therapy.
The first updated draft guidance, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), provides sponsors with recommendations on how to provide sufficient CMC information to ensure safety, identity, quality, purity, and strength/potency of investigational gene therapy products. This guidance applies to gene therapies alone and products that contain a gene therapy in combination with a drug or device.
The second draft guidance, Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus (RCR) during Product Manufacture and Patient Follow-up, provides recommendations regarding the proper testing for RCR during the manufacture of retroviral vector-based gene therapy products, as well as during the follow-up monitoring of patients who have received retroviral vector-based gene therapy products.
The third draft guidance, Long Term Follow-Up (LTFU) After Administration of Human Gene Therapy Products, provides recommendations regarding the design of LTFU observational studies for the collection of data on delayed adverse events after gene therapy.
Once finalized, these draft guidances will replace previous guidances issued by the FDA in April 2008 (CMC) and November 2006 (RCR and LTFU).
The US Food and Drug Administration (FDA) has released several draft guidance documents on gene therapy.
Three are disease-specific guidances—for hemophilia, rare diseases, and retinal disorders—and 3 are guidances on manufacturing gene therapies.
These 6 documents are intended to serve as the building blocks of a modern, comprehensive framework for advancing the field of gene therapy, according to FDA Commissioner Scott Gottlieb, MD.
He said the documents are being issued in draft form so the FDA can solicit public input on these new policies. As with all draft guidances, all comments received will be considered before the FDA finalizes the documents.
Disease-specific guidances
The Human Gene Therapy for Rare Diseases Draft Guidance and the Human Gene Therapy for Retinal Disorders Draft Guidance include considerations for product development, preclinical research, clinical trials, expedited programs, and communication with the FDA.
The Human Gene Therapy for Hemophilia Draft Guidance covers the same topics but also includes considerations for measuring factor VIII and factor IX activity.
The draft guidance for rare diseases encompasses diseases affecting fewer than 200,000 people in the US.
Manufacturing guidances
The 3 remaining draft guidances are actually updates to existing guidances that address manufacturing issues related to gene therapy.
The first updated draft guidance, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), provides sponsors with recommendations on how to provide sufficient CMC information to ensure safety, identity, quality, purity, and strength/potency of investigational gene therapy products. This guidance applies to gene therapies alone and products that contain a gene therapy in combination with a drug or device.
The second draft guidance, Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus (RCR) during Product Manufacture and Patient Follow-up, provides recommendations regarding the proper testing for RCR during the manufacture of retroviral vector-based gene therapy products, as well as during the follow-up monitoring of patients who have received retroviral vector-based gene therapy products.
The third draft guidance, Long Term Follow-Up (LTFU) After Administration of Human Gene Therapy Products, provides recommendations regarding the design of LTFU observational studies for the collection of data on delayed adverse events after gene therapy.
Once finalized, these draft guidances will replace previous guidances issued by the FDA in April 2008 (CMC) and November 2006 (RCR and LTFU).